Eugenol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study design appears to follow OECD guideline 405 (2002) with deviations (purity, pH information, age and body weight of animals, 1 hour observation, individual data and irritation scores were not reported; rationale for in vivo testing not provided; and reversibility effects not determined). Study pre-dates GLP requirements.

Data source

Reference

Reference Type:

review article or handbook

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

purity, pH information, age and body weight of animals, 1 hour observation, individual data and irritation scores were not reported; rationale for in vivo testing not provided; and reversibility effects not determined

Principles of method if other than guideline:

The Draize irritation procedure was applied.:
J.H. Draize, “Dermal toxicity”, in Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, publ., The Association of Food and Drug Officials of the United States, 1959, p. 51.

GLP compliance:

not specified

Remarks:

Study pre-dates GLP requirements

Test material

Test material information

Constituent 1

Reference substance name:

Eugenol

EC Number:

202-589-1

EC Name:

Eugenol

Cas Number:

97-53-0

Molecular formula:

C10H12O2

IUPAC Name:

2-methoxy-4-(prop-2-en-1-yl)phenol

Details on test material:

- Name of test material (as cited in study report): eugenol, 2-methoxy-4-allylphenol

The test articles were stored in brown glass bottles at room temperature (23°C) and were tested within a period of 6 months from the date of receipt.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Animals used for the eye irritation study were female albino rabbits of the New Zealand strain. The rabbits were individually housed in stainless steel cages having a wire mesh floor measuring 16” x 19”; the rack in which they were housed was of the self-flushing variety. The animals received food (Teklad Rabbit Feed) and water ad libitum and were housed in a room controlled for temperature (20°C), humidity (50%) and lighting cycle.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated eye served as the control.

Amount / concentration applied:

Instillation of 0.1 mL of the test material.

Duration of treatment / exposure:

Single application.

Observation period (in vivo):

All eyes were examined 24, 48, and 72 hours and at four and seven days after dosing.

Number of animals or in vitro replicates:

6 healthy female

Details on study design:

Single application. Instillation of 0.1 ml of the test material into the right eye of the animal was accomplished by retracting the lower lid, delivering the dose from a 1cc syringe and holding the upper and lower lids together for several seconds to allow the liquid to mix with the eye fluids. The left remained untreated to serve as a control for the treated eye. Each eye was graded according to the criteria reported in "illustration".

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1 day

Score:

54

Max. score:

110

Reversibility:

not fully reversible within:

Remarks on result:

other: Reversibility effects not determined

Results 2

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 2 days

Score:

27

Max. score:

110

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Reversibility effects not determined

Results 3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 3 days

Score:

20

Max. score:

110

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Reversibility effects not determined

Results 4

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 4 days

Score:

14

Max. score:

110

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Reversibility effects not determined

Results 5

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 7 days

Score:

3

Max. score:

110

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Reversibility effects not determined

Results 6

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable because of methodological limitations

Results 7

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable because of methodological limitations

Results 8

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable because of methodological limitations

Results 9

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable because of methodological limitations

Irritant / corrosive response data:

The overall irritation score decreased from 54 (Day 1) to 3 (Day 7). The scores were gradually decreased over the 7-day study period; however, the full reversibility effects were not determined.

Applicant's summary and conclusion

Interpretation of results:

Category II

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Test article appeared to affect the rabbit eyes 1 day following application; however, the effects were reversible as the eye irritation grades decreased over the 7-day observation period.
This eye irritation information for eugenol is based on the standard Draize scale which has an overall score based on a 110 point rating scale. This rating scale is not directly compatible with Regulation (EC) No 1272/2008, Annex I section 3.3 classification criteria. However, based on guidance from various agencies, eugenol appears to be severely irritating in the first 24 hours post-exposure, moderately to mildly irritating after 24 and 72 hours post-exposure, and practically non-irritating after 7 days post-exposure.

Executive summary:

The potential for eye irritation following exposure to eugenol was assessed in 6 female rabbits (0.1 mL of undiluted eugenol). Observations were carried out at regular intervals over 7 days following exposure. Eugenol appeared to affect the rabbit eyes 1 day following application; however, the effects were reversible as the eye irritation grades decreased over the 7-day observation period.

This eye irritation information for eugenol is based on the standard Draize scale which has an overall score based on a 110 point rating scale. This rating scale is not directly compatible with Regulation (EC) No 1272/2008, Annex I section 3.3 classification criteria. However, based on guidance from various agencies, eugenol appears to be severely irritating in the first 24 hours post-exposure, moderately to mildly irritating after 24 and 72 hours post-exposure, and practically non-irritating after 7 days post-exposure.